The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

PURPOSE: Radiation-induced acute coronary events (ACEs) may occur as a treatment-related late adverse effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remain to be determined. The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in patients with BC treated with radiation therapy. METHODS AND MATERIALS: The study cohort consisted of 910 patients with BC treated with postoperative radiation therapy after breast-conserving surgery. In total, 163 patients had an atherosclerotic plaque in the LAD. The endpoint was the occurrence of an ACE after treatment. For each individual patient, the mean heart dose, volume of the left ventricle receiving ≥5 Gy (LV-V5), mean LAD dose, and mean dose to calcified atherosclerotic plaques in the LAD, if present, were acquired based on planning computed tomography scans. Cox regression analysis was used to analyze the effects on the cumulative incidence of ACEs. RESULTS: The median follow-up time was 9.2 years (range, 0.1-14.3 years). In total, 38 patients (4.2%) developed an ACE during follow-up. For patients with an atherosclerotic plaque (n = 163), the mean dose to the atherosclerotic plaque was the strongest predictor for ACEs, even after correction for cardiovascular risk factors (hazard ratio [HR], 1.269; 95% CI, 1.090-1.477; P = .002). The LV-V5 was associated with ACEs in patients without atherosclerotic plaques in the LAD (n = 680) (HR, 1.021; 95% CI, 1.003-1.039; P = .023). CONCLUSIONS: The results of this study suggest that radiation dose to pre-existing calcified atherosclerotic plaques in the LAD is strongly associated with the development of ACEs in patients with BC.

Role of boost radiotherapy for local control of pure ductal carcinoma in situ after breast-conserving surgery: a multicenter, retrospective study of 622 patients.

PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Sweet syndrome induced by radiations during breast cancer treatment.

During the follow-up of a woman treated by radiotherapy for an in situ carcinoma of her left breast, radio-induced skin lesions were diagnosed. They appeared not to be simple radiodermatitis but radio-induced Sweet syndrome. Discussions were led on the benefit of completing the last session of radiotherapy for such a low-grade malignancy while considering the risk of complication from radio-induced disease. General and local corticotherapy rapidly eradicated the fever and asthenia, while the skin lesions disappeared gradually. Moreover, biological improvement was noticed. The presented features of Sweet syndrome are almost similar in their initial phase to the radiodermatitis that is seen in common medical conditions.

Daily Fractionation of External Beam Accelerated Partial Breast Irradiation to 40 Gy Is Well Tolerated and Locally Effective.

PURPOSE: Most studies examining accelerated partial breast irradiation (APBI) have used twice-daily fractionation. Cosmesis with this approach has produced mixed results, and the optimal fractionation scheme remains unknown. We sought to evaluate the safety and efficacy of APBI with a total dose of 40 Gy in 10 daily fractions. METHODS AND MATERIALS: Between 2010 and 2014, we prospectively enrolled 106 patients to receive APBI after lumpectomy for invasive or in situ node-negative breast cancer. Radiation was administered via 3-dimensional conformal techniques. RESULTS: The median age was 62 years (range, 39-85), and all patients underwent APBI per protocol. With a median follow-up of 58 months, we evaluated patient-reported local toxicity and recurrence outcomes. Of 106 patients, 16 (15%) experienced grade ≥2 skin toxicity. The most common significant toxicities were acute cutaneous changes at 4 to 9 weeks after radiation therapy, including grade 2 erythema in 2 patients (1.8%) and skin color changes in 4 patients (3.8%). Only 2 instances of grade 3 toxicity were reported, including 1 patient with acute moist desquamation after radiation therapy and another with fibrosis at 2 years. Planning target volume and breast V20 were significantly predictive of skin/subcutaneous toxicity, with evidence that limiting breast V20 to <45% may improve tolerability. Overall, 3 breast cancer recurrences arose: 1 local recurrence in the original quadrant (3 years after APBI), 1 in a different ipsilateral quadrant (5 years after APBI), and 1 with distant disease 2 years after APBI. CONCLUSIONS: In an appropriately selected group of patients with early stage breast cancer, APBI to a dose of 40 Gy in 10 daily fractions was well tolerated, with most patients (99%) reporting excellent/good cosmesis. Planning target volume and breast V20 should be carefully constrained to limit local morbidity. Longer follow-up will be needed to establish efficacy and subsequent local recurrence rates.

Three-Fraction Intracavitary Accelerated Partial Breast Brachytherapy: Early Provider and Patient-Reported Outcomes of a Novel Regimen.

PURPOSE: To report early adverse events and patient-reported outcomes (PROs) of 3-fraction intracavitary catheter-based partial breast brachytherapy (ICBB). MATERIALS AND METHODS: Eligible women ≥50 years of age with ≤2.5-cm, lymph node-negative invasive or in situ breast cancer underwent breast-conserving surgery and placement of a brachytherapy applicator. ICBB was initiated on the second weekday after surgery and prescribed to 21 Gy in 3 once-daily fractions. Common Terminology Criteria for Adverse Events, version 4.0; 10-point linear analog scale assessment; the PRO version of the Common Terminology Criteria for Adverse Events; and the Harvard Breast Cosmesis Scale were used for provider and patient-reported assessments. RESULTS: Seventy-three women were treated for invasive (79%) or in situ (21%) breast cancer. The median time to completion of surgery and radiation therapy was 6 days. After 14-months median follow-up, 2 patients (3%) had developed breast infections that resolved with oral antibiotics. There was no other treatment-associated adverse event grade ≥2. The grade 1 seroma rate at 3 months was 20%, which dropped to 8% at 12 months; no events required intervention. At 12 months, 91% of patients reported an overall quality of life score as ≥8 of 10, and patient-reported cosmesis was good or excellent in 95%. All patients are alive without relapse at the last follow-up. CONCLUSIONS: Three-fraction ICBB is associated with low rates of early provider and patient- reported adverse events and compares favorably with early outcomes of more protracted ICBB regimens, including twice-daily (3.4 Gy × 10) fractionation studied in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39. Further investigation is warranted.

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation.

PURPOSE: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. METHODS AND MATERIALS: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohort to 40 Gy. RESULTS: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. CONCLUSION: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.

[Normofractionated breast irradiation in breast cancer. Indications and benefits]. / Irradiation normofractionnée des cancers du sein. Indications et bénéfices.

Whole-breast normofractionated irradiation following breast-conserving surgery is the reference treatment. It delivers a dose of 50Gy in 25 fractions of 2Gy to the reference point, and, in some patients, an additional dose of 16Gy in 8 fractions of 2Gy in the tumor bed. Long-term results and toxicity of this irradiation scheme was prospectively evaluated in several randomised trials and meta-analyses, in invasive cancers as well as in ductal carcinoma in situ. The average 10-year rate of in breast recurrences was 6 % in these trials, with limited cardiac and pulmonary toxicity and limited rate of severe fibrosis. Identification of risk factors of recurrences may help to design new irradiation schemes adapted to tumor biology. The new irradiation schemes must be rigorously evaluated in the long-term in the frame of prospective clinical trials, in order to validate them as new standards of treatment.

Prospective analysis of toxicity in patients treated with strut-adjusted volume implant for early-stage breast cancer.

PURPOSE: We report the toxicity of patients treated with strut-adjusted volume implant (SAVI) for accelerated partial breast irradiation treated at our institution. METHODS AND MATERIALS: Patients treated from January 2013 to July 2015 with SAVI planned for 10 b.i.d. fractions for a total dose of 34 Gy were included. Acute and late toxicities were prospectively collected on patients in followup and graded by the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: A total of 132 patients were included, with 1 patient having synchronous breast cancer treated in each breast. Median followup was 20.0 months (range, 2.7-37.4 months). The median age at diagnosis was 61 years (range, 41-83 years). Forty-two lesions (32%) were in situ, 88 lesions (66%) were Stage 1, and 3 (2%) lesions were Stage 2. The median planning target volume was 58.2 cc (range, 24.2-109.9 cc), median V150 was 26.3 cc (range, 11.5-47.5 cc), and median V200 was 13.0 cc (range, 6.3-26.1 cc). On a pain scale of 0-10 (10 = worst pain), pain was worst on Day 2 of treatment, with an average score of 0.46. There was one acute skin infection; there were three late skin infections, two of which was Grade 3. Other late toxicities were Grade 1 or 2: hyperpigmentation (44%), telangiectasia (0.8%), seroma (9%), fat necrosis (5%), and fibrosis (12%). Crude local recurrence rate was 4%. CONCLUSION: SAVI is a safe treatment option for patients who are candidates for accelerated partial breast irradiation. Local control seems to be excellent, but longer followup is needed.

Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ.

BACKGROUND: The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. METHODS: Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. RESULTS: DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. CONCLUSIONS: Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society.

Ductal Carcinoma In Situ of the Breast: Should Breast Irradiation Be Routinely Added to Surgical Excision?

Confusion exists among women with a new diagnosis of ductal carcinoma in situ and their physicians regarding choice of treatment. The press has accused the medical community of overtreatment and found many physicians eager to support or deny the charge. Improvements in treatment delivery have been matched with better definitions of risk on the basis of biology as defined by genomic analysis rather than only lesion size, margins, receptor status, and patient age. Understanding both the risk of a specific ductal carcinoma in situ progressing to invasive breast cancer and the risks of the treatment options allows tailored recommendations.